A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis.
A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis.
复制标题
果蝇卵子发生过程中，翻译控制模块协调生殖干细胞分化和核糖体生物发生。
DOI：
10.1016/j.devcel.2022.03.005
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发表时间：
2022-04-11
影响因子：
11.8
通讯作者：
Rangan, Prashanth
中科院分区：
文献类型：
--
作者：
Martin, Elliot T.;Blatt, Patrick;Nguyen, Elaine;Lahr, Roni;Selvam, Sangeetha;Yoon, Hyun Ah M.;Pocchiari, Tyler;Emtenani, Shamsi;Siekhaus, Daria E.;Berman, Andrea;Fuchs, Gabriele;Rangan, Prashanth
核糖体缺陷干扰干细胞分化，引起核糖体病。核糖体水平如何控制干细胞分化尚不完全清楚。在这里，我们发现三个DExD/H-box蛋白控制核糖体生物发生（RiBi）和果蝇卵子发生。这些DExD/H-box蛋白的丢失，我们命名为Aramis，Athos和Porthos，异常稳定p53，阻止细胞周期，并阻止GSC分化。Aramis通过调节在其5 '-UTR中含有末端寡嘧啶（TOP）基序的mRNA的翻译来控制细胞周期进程。我们发现TOP基序赋予敏感性的核糖体水平介导的镧相关蛋白（Larp）。一种这样的含有TOP的mRNA编码新核仁蛋白1（Non 1），一种保守的p53去稳定蛋白。在足够的核糖体浓度下，Non 1表达并通过p53降解促进GSC细胞周期进展。因此，果蝇中以前未被重视的TOP基序响应于减少的RiBi以共同调节核糖体蛋白和p53阻遏物的翻译，将RiBi与GSC分化偶联。干细胞分化对核糖体生物合成敏感，但核糖体生物合成如何与干细胞分化偶联尚未完全阐明。Martin等人描述了一种将核糖体蛋白的产生与细胞周期进程相结合以允许雌性果蝇GSC成功分化的途径。
Ribosomal defects perturb stem cell differentiation, causing ribosomopathies. How ribosome levels control stem cell differentiation is not fully known. Here we discovered that three DExD/H-box proteins govern ribosome biogenesis (RiBi) and Drosophila oogenesis. Loss of these DExD/H-box proteins, which we named Aramis, Athos and Porthos, aberrantly stabilized p53, arrested the cell cycle, and stalled GSC differentiation. Aramis controls cell cycle progression by regulating translation of mRNAs containing a Terminal Oligo Pyrimidine (TOP) motif in their 5’-UTRs. We find TOP motifs confer sensitivity to ribosome levels mediated by La-related protein (Larp). One such TOP-containing mRNA codes for Novel Nucleolar protein 1 (Non1), a conserved p53 destabilizing protein. Upon a sufficient ribosome concentration, Non1 is expressed and promotes GSC cell cycle progression via p53 degradation. Thus, a previously unappreciated TOP-motif in Drosophila responds to reduced RiBi to co-regulate the translation of ribosomal proteins and a p53 repressor, coupling RiBi to GSC differentiation. Stem cell differentiation is sensitive to ribosome biogenesis but how ribosome biogenesis is coupled to stem cell differentiation is not fully elucidated. Martin et al. describe a pathway that couples production of ribosomal proteins and cell cycle progression to allow for female Drosophila GSCs to successfully differentiate.
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影响因子：
5.3
作者：
Granneman, S;Bernstein, KA;Baserga, SJ
通讯作者：
Baserga, SJ
影响因子：
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Rangan, Prashanth
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2.7
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通讯作者：
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